Expiratory flow limitation relates to symptoms during COPD exacerbations requiring hospital admission.

BACKGROUND: Expiratory flow limitation (EFL) is seen in some patients presenting with a COPD exacerbation; however, it is unclear how EFL relates to the clinical features of the exacerbation. We hypothesized that EFL when present contributes to symptoms and duration of recovery during a COPD exacerbation. Our aim was to compare changes in EFL with symptoms in subjects with and without flow-limited breathing admitted for a COPD exacerbation. SUBJECTS AND METHODS: A total of 29 subjects with COPD were recruited within 48 hours of admission to West China Hospital for an acute exacerbation. Daily measurements of post-bronchodilator spirometry, resistance, and reactance using the forced oscillation technique and symptom (Borg) scores until discharge were made. Flow-limited breathing was defined as the difference between inspiratory and expiratory respiratory system reactance (EFL index) greater than 2.8 cmH2O·s·L(-1). The physiological predictors of symptoms during recovery were determined by mixed-effect analysis. RESULTS: Nine subjects (31%) had flow-limited breathing on admission despite similar spirometry compared to subjects without flow-limited breathing. Spirometry and resistance measures did not change between enrolment and discharge. EFL index values improved in subjects with flow-limited breathing on admission, with resolution in four patients. In subjects with flow-limited breathing on admission, symptoms were related to inspiratory resistance and EFL index values. In subjects without flow-limited breathing, symptoms related to forced expiratory volume in 1 second/forced vital capacity. In the whole cohort, EFL index values at admission was related to duration of stay (Rs=0.4, P=0.03). CONCLUSION: The presence of flow-limited breathing as well as abnormal respiratory system mechanics contribute independently to symptoms during COPD exacerbations.

Changes in oscillatory impedance and nitrogen washout with combination fluticasone/salmeterol therapy in COPD.

INTRODUCTION: Combination inhaled corticosteroid/long-acting bronchodilator (ICS/LABA) therapy reduces the exacerbation rate and improves spirometry and quality of life in COPD. We hypothesized that ICS/LABA therapy also improves small airway function measured by FOT. METHODS: 14 subjects with COPD were commenced on combination fluticasone propionate/salmeterol therapy for 3 months. At baseline, subjects completed the St George Respiratory Questionnaire (SGRQ) and underwent standard pulmonary function tests as well as forced oscillation technique (FOT) and single and multiple breath nitrogen washouts. All tests were repeated at the completion of 3 months of therapy. RESULTS: Subjects were of mean (SD) age 65.9 years (8.4), BMI 30.0 (5.6), pack years 51.4 (21.1), post-bronchodilator FEV1% predicted 62.7 (20). At baseline, mean SGRQ total was 39.0 (17.7) and FRC% predicted 125.4 (31.3). From FOT, Rrs-total was 5.69 (1.29) cmH2O/L/s, Xrs-total -3.48 (2.16) cmH2O/L/s, EFL Index 3.51 (2.45) cmH2O/L/s. After 3 months of therapy, there were significant improvements in SGRQ score (-13.81, p < 0.0001) despite no change in FEV1 (+40 mL, p = 0.14). From FOT, total resistance (-0.63 cmH2O/L/s, p = 0.0004), reactance (+1.2 cmH2O/L/s, p = 0.013), and expiratory flow limitation (-1.21 cmH2O/L/s, p = 0.02) also improved. There were no significant changes in ventilation heterogeneity indices. CONCLUSION: Combination therapy is associated with improvements in small airways function in COPD, despite an absence of change in FEV1. FOT may be a clinically useful marker of small airway function in COPD that is responsive to treatment.

Day-to-day variability of oscillatory impedance and spirometry in asthma and COPD.

Variability in airway function may be a marker of disease activity in COPD and asthma. The aim was to determine the effects of repeatability and airway obstruction on day-to-day variability in respiratory system resistance (Rrs) and reactance (Xrs) measured by forced oscillation technique (FOT). Three groups of 10 subjects; normals, stable asthmatic and stable COPD subjects underwent daily FOT recordings for 7 days. Mean total and inspiratory Rrs and Xrs, and expiratory flow limitation (EFL) Index (inspiratory - expiratory Xrs), were calculated. The ICC's were high for all parameters in all groups. Repeatability, in terms of absolute units, correlated with airway obstruction and was therefore lowest in COPD. Day-to-day variability was due mostly to repeatability, with a small contribution from the mean value for some parameters. FOT measures are highly repeatable in health, stable asthma and COPD in relation to the wide range of measures between subjects. For home monitoring in asthma and COPD, either the coefficient of variation or individualized SDs could be used to define day-to-day variability.

The feasibility of home monitoring of impedance with the forced oscillation technique in chronic obstructive pulmonary disease subjects.

Respiratory system resistance (Rrs) and reactance (Xrs) measured by forced oscillation technique (FOT) can be potentially used for home monitoring in COPD. Our aims were to determine the technical acceptability, adherence and variability of unsupervised, home FOT measurements over ten consecutive days. Supervised spirometry and FOT measurements were made on ten clinically stable COPD subjects at their homes at the study initiation. Subjects then self-recorded FOT twice daily for ten consecutive days with data transmitted to the laboratory server via a 3G mobile network. Subjects had a mean (SD) age of 68(8) years, smoking history 38.4(8.7) pack/years, post-bronchodilator FEV1 42.4(12.0)% predicted, FEV1/FVC ratio 0.45(0.10), mean Rrs 121.7(26.1)% predicted and mean Xrs 746.8(330.3)% predicted. The supervised measurements of mean Rrs and mean Xrs were similar to the unsupervised measurements (p = 0.34 and p = 0.92, respectively). 197 of 200 possible measurements were transmitted, all of which were deemed to be technically acceptable. The within-subject standard deviation, Sw, of Rrs-total and Xrs-total were 0.47 and 1.0 cmH(2)O L s(-1), respectively. Subjects who have COPD make reliable, unsupervised FOT measurements at home with a high degree of adherence. The day-to-day variability of FOT measurements was similar to that of supervised laboratory recordings. These results support the conduct of larger, longer-term studies of FOT monitoring in COPD.

The relationship between airflow obstruction, emphysema extent, and small airways function in COPD.

BACKGROUND: The severities of COPD (FEV(1) % predicted) and airflow obstruction (FEV(1)/FVC) are considered to be due to both emphysema and small airways disease. To our knowledge, this has not been previously confirmed by combined measurements of emphysema and of small airway function. We hypothesized that small airways disease and emphysema extent contribute independently to the severity of both COPD and airflow obstruction. METHODS: Twenty-six subjects with COPD underwent measurements with forced oscillation technique (FOT) at 6 Hz and single-breath nitrogen washout. Respiratory system resistance, respiratory system reactance (Xrs), and expiratory flow limitation (EFL) index (measured as mean inspiratory Xrs − expiratory Xrs) were derived from FOT. Closing volume/vital capacity (CV/VC) was derived from the washout. Emphysema extent was measured as low attenuation areas < -910 Hounsfield units, expressed as a percentage of CT scan lung volume from multislice CT scans taken at total lung capacity. RESULTS: Subjects were aged (mean ± SD) 69.6 ± 8.0 years. Postbronchodilator FEV(1) was 64.8 ± 19.8% predicted, and diffusing capacity of lung for carbon monoxide was 50.7 ± 15.8% predicted. Emphysema extent was 22.6% ± 15.0% CT scan volume. CV/VC was 16.9% ± 7.9%; Xrs, -3.72 ± 3.03 cm H(2)O/L/s; and EFL index, 3.88 ± 3.93 cm H(2)O/L/s. In multiple regression analyses, FEV(1)/FVC was predicted by both emphysema and CV/VC (model r(2) = 0.54, P < .0001) whereas FEV(1) % predicted was predicted by emphysema and EFL index (model r(2) = 0.38, P = .0014). CONCLUSIONS: The severities of COPD and airflow obstruction are independently predicted by both small airways disease and emphysema extent.